OP-3136 for Cancer

Recruiting at 7 trial locations

Overseen By Olema Medical Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Olema Pharmaceuticals, Inc.

Must be taking: Endocrine therapy, CDK4/6 inhibitor

Disqualifiers: CNS metastases, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment, OP-3136 (experimental treatment), to evaluate its safety and effectiveness. The goal is to determine the optimal dose and assess its use alone and in combination with other cancer drugs like fulvestrant and palazestrant. It targets individuals with advanced solid tumors, including specific types of breast, prostate, or lung cancer that have not responded to other treatments. A suitable candidate might have advanced ER+ HER2- breast cancer or prostate cancer and have tried other treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants must have received certain prior therapies, which suggests that some medications might be continued. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that OP-3136 is still undergoing testing to ensure its safety for people. Most current knowledge comes from early studies examining how the body processes the drug and its effects on the body. Researchers are closely monitoring how well people tolerate OP-3136, both alone and in combination with other cancer drugs like fulvestrant and palazestrant.

For those considering joining the trial, it's important to know that this is the first time OP-3136 is being tested in humans. Detailed safety information is just beginning to be collected. So far, no major safety issues have been reported, but the study remains in its early stages. Participants must stay informed and discuss potential risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cancer, OP-3136 offers a novel approach by targeting unique pathways in cancer cells that current therapies might not address. Researchers are particularly excited about its potential effectiveness as both a standalone treatment and in combination with other agents like fulvestrant and palazestrant. This flexibility in administration could lead to tailored treatment plans that maximize efficacy while minimizing side effects. By exploring different doses and combinations, OP-3136 aims to improve outcomes for patients with metastatic breast cancer (mBC) and metastatic castration-resistant prostate cancer (mCRPC), conditions that often require innovative solutions.

What evidence suggests that OP-3136 could be an effective treatment for cancer?

Studies have shown that OP-3136 might help treat several types of cancer, including ovarian, lung, prostate, and breast cancer. This treatment blocks certain proteins that aid cancer cell growth. In this trial, some participants will receive OP-3136 as monotherapy, while others will receive it with fulvestrant or palazestrant. Early tests indicate that OP-3136, when combined with fulvestrant, is very effective against breast cancer. Even better results occurred when OP-3136 was combined with palazestrant, leading to more significant tumor shrinkage than with fulvestrant. These early findings suggest that OP-3136, either alone or with other drugs, could be promising for treating advanced cancers. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic solid tumors, such as breast, lung, prostate, and non-small cell lung cancer. Participants should have a tumor that has progressed after treatment or be untreatable with standard therapies.

Inclusion Criteria

I have had up to 4 treatments for prostate cancer, including hormone therapy.

My cancer is advanced or metastatic and fits the specific type required.

My cancer cannot be surgically removed, has spread, and no effective treatments are left.

Exclusion Criteria

My advanced cancer has spread to vital organs and poses an immediate risk to my life.

I have been treated with a KAT6A/B inhibitor before.

I have had heart problems or significant heart disease in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluation of safety, tolerability, and PK in a range of doses of OP-3136 to determine the maximum tolerated dose and recommended dose/regimen for expansion

8-12 weeks

Dose Expansion

Evaluation of the recommended dose and regimen from Part 1 in expansion cohorts of participants with ER+ HER2- mBC and mCRPC

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• OP-3136

Trial Overview The study tests OP-3136, an experimental drug targeting specific enzymes (KAT6A/B) in cancer cells. It's conducted in two parts: first to find the right dose (Part 1), then to see how well it works at that dose (Part 2).

How Is the Trial Designed?

Group I: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2 Experimental Treatment 3 Interventions

Group II: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1 Experimental Treatment 3 Interventions

Group III: Part 2A Dose Expansion monotherapy - mCRPC Experimental Treatment 1 Intervention

Group IV: Part 2A Dose Expansion monotherapy - mBC Experimental Treatment 1 Intervention

Group V: Part 1C Dose Escalation in combination with palazestrant Experimental Treatment 2 Interventions

Group VI: Part 1B Dose Escalation in combination with fulvestrant Experimental Treatment 2 Interventions

Group VII: Part 1A Dose Escalation monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Olema Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

970+

Published Research Related to This Trial

The study of OPB-51602, a STAT3 inhibitor, involved 51 patients and established a maximum-tolerated dose (MTD) of 5 mg, with a recommended phase II dose of 4 mg due to tolerability at lower doses.

OPB-51602 showed promising antitumor activity, particularly in patients with non-small-cell lung cancer (NSCLC), with two patients achieving partial responses, highlighting its potential effectiveness in treating refractory solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies. Wong, AL., Soo, RA., Tan, DS., et al.[2022]

The study established that the recommended phase II dose of intraperitoneal (IP) paclitaxel for treating gastric cancer with peritoneal metastasis is 60 mg/m2, as it was well-tolerated with manageable adverse events in 13 patients.

The combination of IP paclitaxel and intravenous FOLFOX showed promising results, with a median overall survival of 16.6 months and a conversion surgery rate of 23.1%, indicating potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intraperitoneal Paclitaxel Plus Intravenous Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) for Gastric Cancer with Peritoneal Metastasis. Kang, SH., Min, SH., Kim, JW., et al.[2022]

In a phase 1 trial involving 24 patients with advanced hepatocellular carcinoma (HCC), OPB-31121, a STAT3 inhibitor, showed limited antitumor activity, with only 25-42.9% of patients achieving stable disease for 8 weeks or more.

The treatment was associated with significant side effects, including nausea, vomiting, and peripheral neuropathy, which raised concerns about the feasibility of long-term use, leading to the conclusion that further development of OPB-31121 for HCC is challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma. Okusaka, T., Ueno, H., Ikeda, M., et al.[2022]

The phase I study of OPB-31121, an oral STAT3 inhibitor, involved 25 patients with advanced solid tumors and established a maximum-tolerated dose (MTD) of 800 mg/day, demonstrating that the drug is safe and relatively well tolerated.

Preliminary results indicated some antitumor activity, with two patients experiencing tumor shrinkage and eight patients maintaining stable disease, suggesting potential efficacy in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors. Oh, DY., Lee, SH., Han, SW., et al.[2022]

OPB-31121, a novel STAT3 inhibitor, effectively downregulated key proteins in the JAK/STAT signaling pathway, leading to reduced cell proliferation and increased apoptosis in gastric cancer cells.

In preclinical models, OPB-31121 demonstrated synergistic effects when combined with standard chemotherapy drugs like 5-fluorouracil and cisplatin, suggesting its potential as a promising treatment option for gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Kim, MJ., Nam, HJ., Kim, HP., et al.[2022]

Citations

1. ir.olema.com ir.olema.com/news-releases/news-release-details/olema-oncology-reports-third-quarter-2025-financial-and

Olema Oncology Reports Third Quarter 2025 Financial and ... Advanced the Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OP-3136, as a monotherapy and in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06784193

NCT06784193 | Phase 1 Study of OP-3136 in Advanced or ... This is a first-in-human, open-label, multicenter phase 1 study to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), ...

3. ir.olema.com ir.olema.com/news-releases/news-release-details/olema-oncology-announces-new-preclinical-data-op-3136

Olema Oncology Announces New Preclinical Data for OP ... These data indicate OP-3136 may be effective in treating ovarian, lung, and prostate cancer indications in addition to breast cancer. A copy of ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/568015

Phase 1 Study of OP-3136 in Advanced or Metastatic Solid ... This is a first-in-human, open-label, multicenter phase 1 study to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), ...

5. globenewswire.com globenewswire.com/news-release/2025/11/10/3184358/0/en/Olema-Oncology-Reports-Third-Quarter-2025-Financial-and-Operating-Results.html

Olema Oncology Reports Third Quarter 2025 Financial and Advanced the Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OP-3136, as a ...

6. ir.olema.com ir.olema.com/node/10051/pdf

Olema Oncology Presents Compelling New Preclinical ... OP-3136 showed robust synergistic anti-tumor activity when combined with fulvestrant or palazestrant as doublet therapy in breast cancer models.

7. firstwordpharma.com firstwordpharma.com/story/5988249

Olema Oncology Reports Second Quarter 2025 Financial ... Report initial clinical results for OP-3136 in 2026. Report top-line data from OPERA-01 in the second half of 2026. Second Quarter 2025 ...

8. trial.medpath.com trial.medpath.com/news/bed7c2d81fd257bf/olema-s-kat6-inhibitor-op-3136-shows-promising-anti-tumor-activity-across-multiple-cancer-types

Olema's KAT6 Inhibitor OP-3136 Shows Promising Anti-Tumor ... The ongoing Phase 1 trial will provide critical data on safety, tolerability, and preliminary efficacy in humans, with results likely to guide ...